Muscular dystrophy refers to a group of genetically determined myopathies characterized by progressive atrophy or degeneration of increasing numbers of individual muscle cells. The structural changes observed histologically are essentially the same in the various types of muscular dystrophies. This may, perhaps, suggest a common etiology. However, the distribution of the affected muscles is quite distinctive. This, along with the mode of inheritance, forms the basis of the classification of these diseases. The muscular dystrophies are traditionally subdivided by the patterns of initial muscle involvement, which in turn correlates fairly well with the type of genetic transmission. The three major forms of muscular dystrophy are as follows: 1) Duchennes Muscular Dystrophy which affects most skeletal muscle groups and is transmitted by an X-linked recessive gene; 2) Limb Girdle Muscular Dystrophy, affecting principally the pelvic and shoulder girdle muscles and is transmitted by an autosomal recessive gene; and 3) Facioscapulohumeral muscular dystrophy, involves the muscles of the face and shoulder girdle and is transmitted by an autosomal dominant gene.
Recently, the defective gene responsible for Duchenne muscular dystrophy (DMD) has been located on the X chromosome. The DMD gene encodes for a large molecular weight protein product called dystrophin. This protein is localized in the sacrolemmal membrane of normal skeletal muscle, but is absent from the skeletal muscle of people with DMD, as well as, dogs and mice with dystrophic muscle. A more benign form of this X-linked recessive disease is Becker's Muscular Dystrophy which is caused by an abnormal DMD gene which encodes an abnormal dystrophin protein. The exact function of dystrophin and the reasons why its absence or abnormal structure results in necrosis of dystrophic muscle fibers has not been determined. However, the amino acid sequence of dystrophin suggests that it is a membrane cytoskeletal protein.
The present technology for initial detection and diagnosis of Duchenne or Becker's Muscular Dystrophy relies on the use of an immunological probe to identify the presence of dystrophin, the absence of dystrophin, or the abnormal molecular weight or content of dystrophin in human muscle biopsies. Immunological assays, however, are indirect and often plagued by non-specific binding and/or cross-reactivity of the immunological probes (antibodies) with other proteins. Both of these problems can lead to false positive determinations. Conversely, other factors can cause interference with the binding of immunological probes with their target proteins (in this case, dystrophin). This type of problem can cause false negative determinations.